Green tea extracts and their isolated constituents have been described in numerous reports as antineoplastic agents. For example, U.S. Pat. No. 6,428,818 teaches use of green tea extracts with a specific composition as therapeutic agents against various human sarcomas and carcinomas. Green tea extract has previously also been reported to enhance the effect of certain antineoplastic agents, including adriamycin and doxorubicin (e.g., Sugiyama and Sadzuka, 1998, Cancer Lett. 133:19-26, or Sadzuka et al., 1998, Clin. Cancer. Res. 4:153-156). In these studies, green tea in combination with adriamycin inhibited tumor growth in M5076 ovarian sarcoma cells, whereas adriamycin alone did not inhibit tumor growth in those cells. Similar effects were observed with green tea extract and doxorubicin on the same cell line. Green tea extract in combination with doxorubicin also enhances the inhibitory effect on Ehrlich ascites tumors in tumor-bearing mice, presumably by increasing the concentration of doxorubicin concentration in the tumor, but not in normal tissue. Further references to antineoplastic properties of green tea extracts, and especially polyphenon E can be found in Clin. Cancer Res. 2003 Aug. 15; 9(9):3312-9.
In other examples, administration of a pharmacologically effective amount of EGCg has been alleged to reduce the incidence of lung cancer in a mammal (see e.g., U.S. Pat. No. 5,391,568). Moreover, EGCg has also been shown to enhance the effect of certain cancer prevention drugs in vitro. For example, EGCg was demonstrated to enhance the apoptotic effect of sulindac and tamoxifen. In that study, the authors contemplated that EGCg would increase the intracellular concentration of the drugs (Suganuma et al., 1999, Cancer Res. 59:44-47). Further references describe combinations of selected polyphenols (e.g., EGCG and ECG) to treat specific types of cancer as taught in U.S. Pat. No. 6,410,061.
In alternative strategies of treatment and/or prevention of cancer, cyclooxygenase-2 inhibitors (COX-2 inhibitors) are employed as therapeutic agents. For example, U.S. Pat. No. 6,486,204 teaches use of certain COX-2 inhibitors drug as therapeutic agents in the treatment of prostate cancer. Similar uses of selected COX-2 inhibitors are reported in U.S. Pat. Nos. 6,552,075 and 6,649,645 in which COX-2 inhibitors are administered as anticancer drugs. Depending on the type of green tea polyphenol, COX-1 or COX-2 may be inhibited with relative good selectivity, resulting in certain therapeutic effects against bladder and prostate cancer as reported in Am. J. Surg. 2004 November; 188(5):505-10 or Int. J. Cancer 2005 Feb. 10; 113(4):660-9.
However, while at least some desirable effect can be obtained using polyphenols or COX-inhibitors, numerous disadvantages remain. Among other things, bioavailability of polyphenols is relatively low as compared to effective in vitro concentrations. Moreover, COX-2 inhibitors tend to have limited effect, unless administered at relatively large dosages. High dosages, however, were recently reported to be implicated in adverse cardiac events.
Thus, while numerous compositions and methods for pharmaceutical agents for treatment and chemoprevention of neoplastic diseases are known in the art, all or almost all of them, suffer from one or more disadvantages. Therefore, there is still a need for improved pharmaceutical agents for treatment and chemoprevention of neoplastic diseases.